Hemotherapy-related cognitive impairment (CRCI) is a significant problem that develops in up to 75% of breast cancer patients, often persisting for many years and significantly impairing quality of life. The etiology of CRCI is not clearly understood, and there are no effective management approaches. Reduction of inflammation is a promising target to alleviate CRCI, and translational investigators well versed in clinical and behavioral research, immunology and neuroscience are needed to advance knowledge in this area. Dr. Michelle Janelsins, an Assistant Professor in the Department of Radiation Oncology at the University of Rochester Medical Center, is applying for a K07 mentored career development award to expand her clinical and behavioral research skills and to integrate new skills with her strong basic science abilities as an independent clinical and translational cancer control investigator with expertise in interventions for CRCI. This application provides Dr. Janelsins with new training and skills necessary to develop, implement, and assess interventions in a clinical setting and combine these new abilities with her established skills and knowledge in immunology and neuroscience to successfully conduct the first randomized, controlled, pilot study we are aware of investigating the influence of two novel interventions (exercise and ibuprofen) on CRCI and inflammation. Career Development Plan: Dr. Janelsins' previous training provides an outstanding initial foundation, but she needs new training in the conduct of Phase II-III clinical trials, cognitive assessment and related bio behavioral immune pathways, and exercise intervention development to become a successful independent clinical researcher with expertise in bio behavioral research focusing on understanding and alleviating CRCI. Her four career development training goals are: 1) to develop expertise in cancer control Phase II-III clinical trials, 2) to develop expertise in cognitive science and cognitive assessments and related bio behavioral immune pathways, 3) to develop expertise in exercise physiology, physical activity assessments and exercise interventions, and 4) to promote the development of an independent academic research career. Dr. Janelsins has an outstanding mentoring team: Dr. Gary Morrow, a leading cancer control researcher with NCI funding for over thirty years, is her senior mentor; Drs. Tim Ahles and Deborah Cory-Slechta provide expertise in neurocognitive testing as her co-mentors; Dr. Karen Mustian provides expertise in exercise interventions as a co-mentor; and advisors Drs. Jan Moynihan (immunology), Michelle Shayne (medical oncology), and Charles Heckler (biostatistics) provide specific expertise in key areas. Research Plan: The proposed Phase II RCT, based partially on Dr. Janelsins' preliminary data, is a three-arm study comparing the influence of ibuprofen + health education (Arm 1), placebo + exercise (Arm 2) and placebo + health education (control; Arm 3) on CRCI in 120 breast cancer patients undergoing chemotherapy experiencing CRCI. The exercise and ibuprofen arms will each be compared to the control (Arm 3) with the primary goal of assessing, analyzing, and interpreting the preliminary efficacy of each intervention in alleviating CRCI and the effects of each intervention on inflammation. This award will position Dr. Janelsins to become a leader in the cancer and cognition field who, over her career, will make meaningful contributions to patient care. Research findings will be used to design future definitive RCTs, ensure Dr. Janelsins' successful transition to an independent, R01- funded, clinical and translational investigator, and ultimately reduce the public health burden from CRCI.